Today, nuclear magnetic resonance is one of the most widely used tools for the detailed elucidation of the structure and dynamics of compounds of chemical and biological interest. In the last few years, the surge of interest in applications of NMR to problems in biology and medicine can be directly attributed to improvements in instrumental and magnet technology and the advent of various two-dimensional NMR methods. In order to accommodate the critical need for these facilities in the research programs of several primary investigators in the Yale School of Medicine, funds are requested in this application for a high field (11.75T) NMR spectrometer that will be housed in the new comprehensive NMR Center at the Yale School of Medicine and dedicated to macromolecular/biomedical NMR research. In support of this application are the research protocols of nine principal investigators from within the Yale School of Medicine requiring state-of-the-art high field NMR, in particular protons at 500 MHz, for the structural characterization of a variety of biologically important macromolecules, their substrates and related metabolic intermediates. Application of NMR in all of the areas proposed has only recently been made possible by the availability of NMR spectrometers operating at fields that are high enough to provide resolution of signals from individual sites within macromolecules or from individual metabolites in the complex mixtures that exist in various biological fluids or cell extracts. The projects outlined in this application cover a broad spectrum of active, ongoing research in biology and medicine for which the proposed use of high field NMR is both essential and not otherwise available.